Abstract PS1-12-18: Treatment with CDK4/6 inhibitors in elderly patients with HR positive/HER2 negative metastatic breast cancer: experience from a Spanish center

Abstract Introduction CDK4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) are the standard first-line treatment for hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer (mBC). However, evidence in elderly patients remains limited. This study aimed to evaluate the efficacy and tolerability of CDK4/6i in elderly (≥70 years) versus younger (<70 years) patients with HR+/HER2- mBC. Methods We conducted a retrospective cohort study of patients treated with CDK4/6i at our center between 2014 and 2023. Clinicopathological data were extracted from electronic medical records. Survival outcomes and safety were assessed and stratified by age. Results A total of 169 patients were included: 116 (68.6%) <70 years (mean age 55.6) and 53 (31.4%) ≥70 years (mean age 76.2). Median follow-up was 44.9 (29.2-75.2) months. Approximately one-third of patients had de novo mBC in both groups. An ECOG performance status of 2 was observed in 13% of patients <70 years and 44% of those ≥70 years (p = 0.001). Aromatase inhibitors were more commonly used in elderly patients, while fulvestrant was more frequent in younger ones (p = 0.03). CDK4/6i were used as first-line in 60% of both groups. A significant difference in CDK4/6i choice was observed (p<0.001): palbociclib was the most frequently prescribed in ≥70 (63.5%), while <70 patients received all three agents equally. The number of cycles and grade 3-4 toxicities were similar; neutropenia was the most common severe toxicity (69%). Disease progression was the main cause of discontinuation (88%). Treatment was discontinued due to toxicity in 11% of <70 and 13% of ≥70 patients (p = NS). After progression, significantly fewer elderly patients received further treatment (92.6% vs 69.8%; p = 0.001) Progression-free survival (PFS) was similar between groups (13.1 vs 11.1 months, p = 0.536), and also among patients treated in first line (p = 0.420). In multivariate analysis, de novo mBC was associated with shorter PFS [HR 1.60 (1.05-2.45); p = 0.03], while first-line CDK4/6i use was linked to longer PFS [HR 0.58 (0.39-0.88); p = 0.009]. Neither age nor CDK4/6i type affected PFS. Overall survival (OS) was shorter in elderly patients (35.9 vs 51.1 months, p = 0.003). Receiving subsequent treatment was associated with improved OS [HR 0.33 (0.17-0.63); p = 0.001]. Conclusions In this real world cohort, palbociclib was the most frequently prescribed CDK4/6i in elderly patients. Toxicity and PFS were comparable across age groups. However, elderly patients had shorter OS, potentially related to reduced access to subsequent treatments and age-related factors. Citation Format: M. López Flores, M. Vázquez Diez, J. A. Fong Gutiérrez, E. Honrado Franco, J. Sáez Hortelano, S. Abella Álvarez, M. Rodríguez García, L. López González, A. López González. Treatment with CDK4/6 inhibitors in elderly patients with HR positive/HER2 negative metastatic breast cancer: experience from a Spanish center [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-12-18.